Several studies have reported the incidence and prognosis related to acute kidney injury (AKI) after transcatheter aortic valve replacement (1). We performed a nationwide cohort study to investigate the incidence of AKI and its relation to mortality and end-stage renal disease (ESRD) in patients who underwent isolated surgical aortic valve replacement (SAVR).

We identified all patients who underwent a primary isolated SAVR between 1999 and 2013 from the SWEDEHEART registry. We excluded patients with kidney transplants or on dialysis. AKI was defined according to Kidney Disease Improving Global Outcomes criteria: stage 1 as a ≥0.3 mg/dl (≥26 μmol/l) or a 1.5- to 1.9-fold increase; stage 2 as a 2.0- to 2.9-fold increase; and stage 3 as a ≥3.0-fold increase in post-operative serum creatinine levels, a serum creatinine level of ≥4.0 mg/dl (≥354 μmol/l), or initiation of renal replacement therapy. Linkage with national health data registries provided vital status and comorbidities. ESRD was defined as initiation of dialysis or kidney transplantation, and was retrieved from the Swedish Renal Registry. Cox regression was used to estimate hazard ratios and 95% confidence intervals for all-cause mortality according to AKI stage. Age was modeled by restricted cubic splines, and all other variables were included as categorical terms. Competing risk regression was used to estimate subdistribution hazard ratios and 95% confidence intervals for ESRD, using death as a competing event. Statistical analyses were performed using Stata version 13.1 (StataCorp, College Station, Texas). The regional ethics committee approved the study.

In total, 9,047 patients were included, and 1,523 (17%) patients developed AKI. Patients with AKI were older and had more comorbidities than patients without AKI. During a mean follow-up of 5.6 ± 3.7 years, 2,109 (23%) patients died and 29 (0.3%) patients developed ESRD (Table 1). Long-term mortality was almost doubled in stage 1 and increased more than 3-fold in stages 2 to 3 AKI. The adjusted relative risk for death was increased by 27% among patients in stage 1 AKI and more than doubled in AKI stages 2 to 3 (Table 1). The incidence and the relative risk of ESRD increased with advancing AKI stage. We found no evidence of effect modification by age, sex, renal function, left ventricular ejection fraction, diabetes, or peripheral vascular disease.

Event Rates and Relative Risk for All-Cause Mortality and End-Stage Renal Disease in Patients Who Underwent Aortic Valve Replacement According to AKI Stage

In a nationwide cohort of 9,047 patients in Sweden who underwent isolated SAVR over a 15-year period, we found that a small increase in post-operative serum creatinine of only ≥0.3 mg/dl (≥26 μmol/l) was associated with a 27% increased risk of death and a >4-fold increased risk of ESRD during follow-up. The increased risk of death or ESRD in patients with AKI was independent of pre-operative renal function and other clinically relevant parameters. The main strength of our study was the nationwide population-based design with complete and accurate follow-up, ensuring a high external validity. The main limitations were that few patients developed ESRD during follow-up, which resulted in low precision in ESRD risk estimates and the possibility of residual confounding. Our findings are interesting, because very few patients had established coronary artery disease and because risk factors for cardiovascular disease were less prevalent than in previous studies on AKI after cardiac surgery that included patients who had coronary artery disease. In the present study, the associations between AKI and increased risk of ESRD were similar to the results of our prior study on AKI after coronary artery bypass graft (CABG) and risk of ESRD (2). Patients who underwent isolated CABG were more often diabetic (23% vs. 14%) and more likely to have had a prior myocardial infarction (45% vs. 8%) compared with patients in the present study (2). These findings strengthen the idea that there may well be a causal relationship between AKI and adverse outcomes and that AKI may not merely be a marker of more advanced atherosclerotic disease. From a clinical perspective, we believe that our findings underscore the need for close monitoring of patients with AKI. This may be especially important for patients who undergo isolated SAVR because they are less likely to receive medication that can prevent deterioration of renal function compared with CABG patients, who often already have guideline-recommended secondary prevention medication.

Footnotes

Please note: This study was supported by the Swedish Medical Society (SLS-330221 to Dr. Sartipy; SLS-177331 to Dr. Holzmann), Karolinska Institutet Foundations and Funds (40842 to Dr. Sartipy), and the Mats Kleberg Foundation (2014-00017 to Dr. Sartipy). Dr. Rydén has reported that she has no relationships relevant to the contents of this paper to disclose. The authors thank the steering committees of the SWEDEHEART and Swedish Renal Registry for providing data for this study. (HeAlth-data Register sTudies of Risk and Outcomes in Cardiac Surgery [HARTROCS]; NCT02276950)

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